Masino Susan A, Kawamura Masahito, Ruskin David N, Gawryluk Jeremy, Chen Xuesong, Geiger Jonathan D
Department of Psychology/Neuroscience Program, Trinity College, Hartford, Connecticut, 06106, USA.
Open Neurosci J. 2010 Jan 1;4(1):58-63. doi: 10.2174/1874082001004010058.
Ketogenic diets are high in fat and low in carbohydrates and represent a well-established and effective treatment alternative to anti-epileptic drugs. Ketogenic diets are used for the management of a variety of difficult-to-treat or intractable seizure disorders, especially pediatric refractory epilepsy. However, it has been shown that this dietary therapy can reduce seizures in people of all ages, and ketogenic diets are being applied to other prevalent medical conditions such as diabetes. Although used effectively to treat epilepsy for nearly 90 years, the mechanism(s) by which ketogenic diets work to reduce seizures remain ill-understood. One mechanism receiving increased attention is based on findings that ketogenic diets increase the brain energy molecule ATP, and may also increase the levels and actions of the related endogenous inhibitory neuromodulator adenosine. ATP and adenosine have both been identified as important modulators of seizures; seizures increase the actions of these purines, these purines regulate epileptic activity in brain, adenosine receptor antagonists are pro-convulsant, and adenosinergic mechanisms have been implicated previously in the actions of approved anti-epileptic therapeutics. Here we will review recent literature and describe findings that shed light on mechanistic relationships between ketogenic diets and the purines ATP and adenosine. These emerging mechanisms hold great promise for the effective therapeutic management of epileptic seizures and other neurological conditions.
生酮饮食富含脂肪且碳水化合物含量低，是一种公认的、有效的抗癫痫药物替代治疗方法。生酮饮食用于治疗各种难治性或顽固性癫痫发作疾病，尤其是小儿难治性癫痫。然而，研究表明这种饮食疗法可以减少各年龄段人群的癫痫发作，并且生酮饮食正被应用于其他常见的医学病症，如糖尿病。尽管生酮饮食有效治疗癫痫已有近90年历史，但其减少癫痫发作的作用机制仍未完全明确。一个受到越来越多关注的机制是基于以下发现：生酮饮食会增加大脑能量分子三磷酸腺苷（ATP），还可能提高相关内源性抑制性神经调质腺苷的水平及作用。ATP和腺苷均已被确定为癫痫发作的重要调节因子；癫痫发作会增强这些嘌呤的作用，这些嘌呤调节大脑中的癫痫活动，腺苷受体拮抗剂具有促惊厥作用，并且腺苷能机制此前已被认为与已批准的抗癫痫治疗药物的作用有关。在此，我们将回顾近期文献，并描述有助于阐明生酮饮食与嘌呤ATP和腺苷之间机制关系的研究结果。这些新出现的机制为癫痫发作及其他神经系统疾病的有效治疗管理带来了巨大希望。
